Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43873   clinical trials with a EudraCT protocol, of which   7292   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-004754-42
    Sponsor's Protocol Code Number:PP06490
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-11-04
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2017-004754-42
    A.3Full title of the trial
    A Phase 3, double-blind, multicenter, placebo-controlled study of PledOx used on top of modified FOLFOX6 (5 FU/FA and Oxaliplatin) to prevent chemotherapy induced peripheral neuropathy (CIPN) in patients with first-line metastatic colorectal cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3, double-blind, multicenter, placebo-controlled study of a new drug, PledOx used on top of standard therapy to prevent damages to nerves of the peripheral nervous system, induced by chemotherapy, in patients suffering from cancer of the large intestine that have spread to other parts of the body
    A.3.2Name or abbreviated title of the trial where available
    POLAR-M
    A.4.1Sponsor's protocol code numberPP06490
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03654729
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPledPharma AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPledPharma AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPledPharma AB
    B.5.2Functional name of contact pointChief Medical Officer
    B.5.3 Address:
    B.5.3.1Street AddressGrev Turegatan 11c
    B.5.3.2Town/ cityStockholm
    B.5.3.3Post codeSE 114 46
    B.5.3.4CountrySweden
    B.5.4Telephone number+46709641 009
    B.5.5Fax number+468663 57 25
    B.5.6E-mailstefan.carlsson@pledpharma.se
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePledOx 50mM
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1401243-67-1
    D.3.9.2Current sponsor codeCalmangafodipir
    D.3.9.3Other descriptive nameCa4Mn(DPDP)5
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number37
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Chemotherapy induced peripheral neuropathy
    E.1.1.1Medical condition in easily understood language
    Damages to nerves of the peripheral nervous system, induced by chemotherapy
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10079545
    E.1.2Term Chemotherapy induced peripheral neuropathy
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare each dose of PledOx (2 and 5 µmol/kg) vs placebo with respect to the proportion of patients with moderate or severe chronic CIPN
    E.2.2Secondary objectives of the trial
    Compare each dose of PledOx vs placebo

    Efficacy
    • Proportion of patients with mild, moderate or severe chronic CIPN
    • Sensitivity to touching cold items
    • Cumulative dose of oxaliplatin during chemotherapy
    • Vibration sensitivity on the lateral malleolus
    • Worst pain in hands or feet
    • Functional impairment (non-dominant hand)
    • Sustained efficacy on prevention of CIPN during LTFU

    Safety
    • Overall response rate
    • Progression-free survival
    • Overall survival
    • Safety and tolerability

    Exploratory
    • Chronic CIPN by supporting analysis using full FACT/GOG NTX-13
    • Cumul. dose of 5-FU during chemo
    • Both oxaliplatin and 5-FU: number of cycles, dose intensity & reductions (reason for reduction), dose delays (length of delay)
    • PK profile of PledOx with multiple dosing*
    • QT/QTc interval using 12-lead ECG*
    • Functional impairment (LTFU)
    • Worst pain in hand or feet during LTFU
    • QoL/health status
    • Health eco impact

    *84 pts (28/group) in preselected sites only
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed informed consent form before any study related assessments and willing to follow all study procedures.
    2. Male or female aged ≥18 years.
    3. Non-resectable metastatic (stage IV) CRC, pathologically confirmed adenocarcinoma of the colon or rectum.
    4. No prior systemic chemotherapy and/or biologic/targeted therapy for metastatic CRC.
    5. Measurable disease according to RECIST 1.1.
    6. Patient indicated for at least 3 months of oxaliplatin-based chemotherapy (without any pre-planned treatment breaks) and without pathological findings of a neurologic exam performed prior to oxaliplatin treatment according to local practice
    7. ECOG performance status of 0 or 1.
    8. Adequate hematological parameters: hemoglobin ≥100 g/L, absolute neutrophil count (ANC) ≥1.5 x 10^9/L, platelets ≥100 x 10^9/L.
    9. Adequate renal function: creatinine clearance >50 cc/min using the Cockroft and Gault formula or measured.
    10. Adequate hepatic function: total bilirubin ≤1.5 times the upper limit of normal (ULN) (except in the case of known Gilbert’s syndrome); AST and ALT ≤3 times ULN (AST and ALT ≤5 times ULN in case of liver metastases).
    11. Baseline blood manganese level <2.0 times ULN.
    12. For patients with a history of diabetes mellitus, HbA1c ≤7%.
    13. Negative pregnancy test for females of child-bearing potential.
    14. For men and females of childbearing potential, use of adequate contraception (oral contraceptives, intrauterine device or surgically sterile) while on study drug and for at least 6 months after completion of study therapy.
    E.4Principal exclusion criteria
    1. Any unresolved toxicity by Common Terminology Criteria for Adverse Events Version (CTCAE v4.03) > Grade 1 from previous anti-cancer therapy (including radiotherapy), except alopecia.
    2. Any grade of neuropathy from any cause.
    3. Any evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renal disease).
    4. Chronic infection or uncontrolled serious illness causing immunodeficiency. Patients with known history of chronic hepatitis B can be enrolled if they are asymptomatic and an acute and active HBV infection can be excluded.
    5. A surgical incision that is not healed.
    6. Significant hemorrhage (>30 mL/bleeding episode in previous 3 months), hemoptysis (>5 mL fresh blood in previous 4 weeks) or thrombotic event (including transient ischemic attack) in the previous 12 months if the patient is expected to receive anti-VEGF/VEGFR therapy.
    7. Known hypersensitivity to any of the components of mFOLFOX6 and, if applicable, biological therapies to be used in conjunction with the chemotherapy regimen or any of the excipients of these products.
    8. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for that other malignancy for at least 2 years.
    9. Known dihydropyrimidine dehydrogenase deficiency.
    10. Pre-existing neurodegenerative disease (e.g., Parkinson’s, Alzheimer’s, Huntington’s) or neuromuscular disorder (e.g., multiple sclerosis, amyotrophic lateral sclerosis, polio, hereditary neuromuscular disease).
    11. Major psychiatric disorder (major depression, psychosis), alcohol and/or drug abuse.
    12. Patients with a history of second or third degree atrioventricular block or a family heredity.
    13. A history of a genetic or familial neuropathy.
    14. Treatment with any investigational drug within 30 days prior to randomization.
    15. Pregnancy, lactation or reluctance to using contraception.
    16. Any other condition that, in the opinion of the investigator, places the patient at undue risk.
    17. Previous exposure to mangafodipir or calmangafodipir.
    18. Welders, mine workers or other workers in occupations (current or past) where high manganese exposure is likely.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients (with moderate or severe chronic CIPN) scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-13 (i.e., FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, 9 months after the first dose of IMP (i.e. PledOx or placebo administered on Day 1, Cycle 1 of mFOLFOX6 chemotherapy).
    E.5.1.1Timepoint(s) of evaluation of this end point
    9 months after first dose of IMP
    E.5.2Secondary end point(s)
    Secondary Endpoints
    Efficacy
    • Proportion of patients (with mild, moderate or severe chronic CIPN) scoring 2, 3, or 4, in at least 1 of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, 9 months after the first dose of IMP.
    • Mean change from baseline in sensitivity to touching cold items on day 2, Cycle 4 of mFOLFOX6 chemotherapy, as assessed by the Cold Sensitivity questionnaire.
    • Mean cumulative dose of oxaliplatin administered per patient during mFOLFOX6 chemotherapy, 9 months after the first dose of IMP.
    • Mean change from baseline in vibration sense, on the lateral malleolus (left and right), using a graduated tuning fork, at 9 months after the first dose of IMP.
    • Mean change from baseline in worst pain in hands or feet in the past week, using a numerical rating scale (NRS), at 9 months after the first dose of IMP.
    • Mean change from baseline in the time to complete the grooved Pegboard with the non-dominant hand, at 9 months after the first dose of IMP.
    • Proportion of patients scoring 3 or 4 in at least 1 of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, 12, 15, 18, 21 and 24 months after the first dose of IMP.

    Safety
    • ORR
    • PFS
    • Time to death (OS)
    • Safety and tolerability as assessed by adverse events (AEs), laboratory variables and vital signs
    • Proportion of patients with PledOx toxicities in addition to chemotherapy-related toxicities graded using the NCI-CTCAE v4.03

    Exploratory Endpoints
    • Proportion of patients with any CIPN scoring 1, 2, 3 or 4, in any of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), targeting numbness, tingling or discomfort in hands and/or feet, at all other timepoints after the first dose of IMP.
    • Mean score of the first 4 items of the FACT/GOG-NTX-13 (i.e. FACT/GOG-NTX-4), at 9 months after the first dose of IMP.
    • Mean score of the 13 items of the FACT/GOG-NTX-13, at 9 months after the first dose of IMP.
    • Mean cumulative dose of 5-FU administered per patient during mFOLFOX6 chemotherapy, 9 months after the first dose of IMP.
    • For both oxaliplatin and 5-FU: Dose intensity, mean number of cycles per patient, proportion of patients with any dose reduction, reason(s) for dose reductions, proportion of patients with any dose delay, and mean duration of dose delay.
    • PK parameters including Cmax, tmax, AUC0-last of PledOx (only at pre-selected sites and in 84 patients in total), at all measured time points.
    • Mean QT/QTc interval using a 12-lead ECG (only at pre-selected sites and in 84 patients in total), at all measured time points.
    • Mean health index and mean VAS score, using the EQ-5D-5L, at 9, 12, 15, 18, 21, and 24 months after the first dose of IMP.
    • Mean health index, using the FACT/GOG, at 9, 12, 15, 18, 21, and 24 months after the first dose of IMP.
    • Mean time to complete the grooved Pegboard, with the non-dominant hand, at 12, 15, 18, 21, and 24 months after the first dose of IMP.
    • Mean change from baseline in worst pain in hands or feet in the past week, using a NRS, at 12, 15, 18, 21, and 24 months after the first dose of IMP.
    • The proportion of patients with a 2-point, 3-point and 4-point increase in worst pain in hands or feet in the past week, using a NRS, at 9, 12, 15, 18, 21, and 24 months after the first dose of IMP.
    • Health economic impact, measured by the combined impact of medical resource utilization (hospitalizations, outpatient visits, medical procedures and medical use), patient impact (AEs, fall accidents, functional loss) and indirect societal costs (loss of ability to work), at 6, 12, 18 & 24 months after the first dose of IMP.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - FACT/GOG-NTX-13, Grooved pegboard, Grad. Tuning fork, Pain NRS: treat visits V1-12 (D1 of each Cyc), assess visits M3, 6, 9, 12, 15, 18, 21 & 24, EoT (D14 last cycle)
    - AEs: V1-12, M3 & 6, EoT
    - PFS & OS: M3, 6, 9, 12, 15, 18, 21 & 24, EoS (OS only)
    - CT/MRI scan: Screen, V4, 8, 12, M9-24
    - Disease assessment: V5, 9, M6-24, EoT
    - Biochem: V1, 3, 5, 7, 9, 11, EoT
    - Blood Mn: Screen, V4, 8, 12, EoT
    - Hemato, Vital sign, ECOG: Screen, V1-12, M3, 6, 9, 12, 15, 18, 21 & 24, EoT
    - Cold sensitivity: Screen, V2, 4 & 8 days 1, 2, 3 after IMP infusion
    - QoL/health status: V1, 4, 8 & 12, M9-24
    - Physical exam: Screen, M6-24, EoT
    - MRI of CNS and Blood Mn incl. neuro exam: V1-12, M3, EoT
    - ECG: Screen
    - PK patients: PK & ECG: V1, 4 & 8 (EoT for ECG)
    - HE: V1, M6, 12, 18 & 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Czech Republic
    France
    Germany
    Hong Kong
    Hungary
    Italy
    Japan
    Korea, Republic of
    Spain
    Taiwan
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Last patient reaching End of Study: Overall Survival assessment at approximately month 36 (by telephone or any available medical source)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months10
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 210
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 210
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 235
    F.4.2.2In the whole clinical trial 420
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-10-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-10-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2020-08-31
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon May 06 18:45:56 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA